This invention concerns centrifuged evaporators and processes for evaporation primarily but not exclusively for separating volatile components from less volatile components of liquid mixtures typically but not exclusively volatile solvents and solvent components in liquid mixtures.
In the preparation of pharmaceuticals and drugs it is a common requirement to separate an unwanted volatile solvent component from less volatile materials and one technique which has been developed involves centrifuging the mixture while simultaneously evacuating the chamber containing the centrifuge material so as to draw off from the mixture the more volatile component and leave the less volatile material behind. Thus chemists and biologists frequently need to remove liquids in which the solid matter in which they are interested is dissolved or suspended. The solid matter may be potential new drugs, biological samples or other materials. They are frequently sensitive to heat, so that the liquid cannot be boiled off at atmospheric pressure because this would involve excessively high temperatures. Boiling, or evaporation under vacuum is often the preferred process because this can be done at low temperatures which do not harm the samples. If samples in liquids are exposed to vacuum the tend to boil vigorously and this activity can lead to liquid containing valuable sample material being spilled and lost, or worse, to cross-contamination of samples which may have just been expensively purified.
It is therefore well known to spin such samples in a closed vacuum chamber so as to subject them to rotation generated centrifugal forces which suppress the spitting or frothing of the liquid while it is boiling under vacuum. This process is known as Centrifugal Evaporation, or Concentration.
A typical arrangement comprises a stationary chamber which can be sealed and evacuated and within which is mounted a rotatable support carrying a number of test tube like containers which are gimbled at their upper ends and which will normally hang vertically when the support is stationary but will swing upwardly and assume a more horizontal attitude as the support is rotated at high speed.
Whilst the chamber is at atmospheric pressure and either contains air or gas at atmospheric pressure, the resistance to motion as the test tube devices are rotated increases particularly as the test tube devices rotate into their more horizontal attitude. This limits the speed of rotation and typically the power units associated with conventional centrifuges have been sufficient to attain a rotational speed of approximately 1,000 RPM whilst the chamber is at or near atmospheric pressure. However as the chamber is evacuated the resistance to rotation decreases and the rotational speed can rise. Thus current practice is to spin the samples as fast as can be achieved, with conventional drive motors at atmospheric pressure, before evacuating the chamber. This is typically about 1000 RPM which might provide a centrifugal force of around 150 g. The chamber is then evacuated and the rotor spins faster as the pressure drops due to the reduction in drag caused by the residual air in the chamber, and most equipment in use achieves a final rotor speed in the range 1350-1750 RPM at vacuum.
After the process is completed, the chamber is repressurised to atmospheric pressure and the motor is run down, and as the apparatus becomes stationary the gimbled test tube devices rotate into their vertical mode and can be removed.
Whilst apparatus and a method of operation such as described has proved satisfactory for some solvent containing mixtures, a problem has arisen where such apparatus and method has been used to remove two solvent components from such a mixture, where the solvent components have different volatilities and different specific gravities. In this case unpredictable behaviour has been observed coupled with spitting and uncontrolled emission of one or both of the components, which can cause contamination if it enters some of the other test tube devices instead of being systematically and cleanly evacuated from the chamber. In particular, the known process is not appropriate for mixtures of liquids consisting of a dense volatile liquid such as dichloromethane (DCM), or chloroform, mixed with less dense and less volatile liquids such as methanol. It is found that severe spitting leading to sample loss and cross-contamination can occur with such liquid mixtures, under the same conditions in which neither liquid will spit if processed alone.
This can even occur where the mixture of the liquids is homogeneous and the solvents are fully miscible so that no segregation occurs under the action of centrifugal force. However as soon as a partial vacuum is applied, preferential evaporation of the more volatile component takes place from the surface of the mixed liquid, leaving the top layer depleted in that liquid and therefore less dense and less volatile than the bulk liquid below. It therefore forms a non-evaporating liquid blanket, which prevents the bulk liquid evaporating. If the pressure in the chamber is then lowered further the bulk liquid becomes superheated because, although its temperature may not change, the lowered pressure has the effect of raising the temperature of the liquid above its boiling temperature. This causes it to boil very vigorously as nuclei are formed. This boiling bulk liquid penetrates the liquid blanket and leaves the container, causing sample loss and the possibility of cross-contamination.
It is an object of the present invention to provide an improved apparatus and method for centrifugal evaporation of solvent mixtures so as to obviate the identified problem.
According to one aspect of the present invention there is provided a method of evaporating a mixture of liquids having different volatilities and different specific gravities from a mixture in a container of such liquids and other non-volatile materials, comprising the steps of centrifuging the mixture whilst still under a positive pressure, as opposed to a vacuum, at a sufficiently high speed of rotation before evaporation of the more volatile component occurs, and only thereafter progressively evacuating a sealable chamber enclosing the container, so as to reduce the pressure and cause the volatile components to evaporate under the reduced pressure conditions.
The chamber may be returned to normal pressure after the volatile components have been evaporated and collated, after which the rotating device is run down to allow the material left in the containers to be collected.
The invention constrains the different components of the mixture and ensures a more controlled evaporation than would occur at lower rotation-generated centrifugal forces.
Existing apparatus is not capable of performing this method since the motor power hitherto provided in evaporating centrifuges has been insufficient to spin the material to be centrifuged at a sufficiently high speed in a gaseous environment in which the gas pressure is sufficiently high to prevent evaporation of the more volatile component before the pressure is reduced.
According to another aspect of the present invention, apparatus for performing the above method comprises a sealable chamber and vacuum pump associated therewith to enable the chamber to be evacuated, a motor for rotating a support within the chamber, at least one container mounted on the support for containing a mixture of materials having differing volatilities and specific gravities, and a control system for controlling the operation of the apparatus, wherein the power of the motor is sufficient to rotate the support and the container at a sufficiently high speed before the pressure in the chamber is lowered below that at which the more volatile component will evaporate to prevent unwanted agitated boiling of more dense volatile components from the mixture.
In practice the motor will in general need to provide sufficient torque to be able to rotate the assembly faster, at a moderate positive pressure of say xc2xd atmosphere, than it is required to rotate the assembly at full vacuum.
Sensors may be provided for indicating to the control system the pressure within the chamber, the rotational speed of the support within the chamber, the solvent content of the gases in or leaving the chamber during the evacuation thereof, and the temperature of the liquid mixture in the container.
Programmable means may be provided for supplying power to the motor to rotate the support and the container, and for operating the vacuum pump to the chamber only after the speed sensor indicates that a sufficient rotational speed has been achieved.
Means may be provided for removing the vacuum as by slowly shutting down the vacuum pump or slowly by-passing the latter to allow the pressure within the chamber to slowly revert to atmospheric pressure, and to remove power from the motor in a controlled manner to allow the assembly to run down, and if provided, to apply controlled braking to the rotatable support to reduce its rotational speed, albeit in a controlled manner.
An interlock is preferably provided such that centrifuging and evacuation cannot be performed unless the chamber has been closed and sealed.
The process may be automated by means of a process timer or by using information derived from a sensor in the feed to the vacuum pump such that the evacuation process is only terminated after a predetermined low level of solvent concentration in the gaseous mixture, has been attained.
The containers containing the materials which are to be centrifuged may be in the form of test tubes which are gimbled near their open upper end to the support by which they can be rotated, and which normally hang in a generally vertical manner but with rotation assume a generally horizontal mode with the closed end of each tube outermost, the liquid in the tube being constrained to remain at the closed end of the tube due to the forces generated by the rotation.
Alternatively each rotatable container may comprise a chamber containing a well for the liquid contents and an inclined surface leading from the lower region of the well to a radially outwardly displaced elevated region of the chamber up and along which the liquid contents flow so as to enter the elevated region under the forces generated during rotation, and from which region the liquid mixture will flow down to return to to the well as the rotational speed drops, and the forces due to rotation diminish.
Such alternative chambers obviate the need for gimballed test-tube like devices.